The objective of this proposal is to determine pharmacological and biochemical correlates of the activity of high-dose ara-C in acute leukemia and to use this information to predict patient response and duration of remission. The leukemic cells to be studied will be derived from two populations of patients with acute leukemia: (a) those who have not previously received chemotherapy, or (b) those who either failed primary induction therapy or who have relapsed after attaining a complete remission. Studies will be conducted on the leukemic bone marrow and peripheral blood cells of patients during treatment with high-dose ara-C to determine the pharmacodynamics of the active metabolite ara-CTP, its relationship to the competing metabolite, dCTP, and the effect of the concentration of each of these nucleotides on cellular DNA synthesis. Studies will also be conducted on leukemia cells in vitro before beginning chemotherapy next time to determine the extent of the incorporation of ara-C nucleotides into DNA and the ability of the cells to accumulate and retain ara-CTP. This proposal is viewed as an opportunity to evaluate several tumor-specific metabolic parameters of a single therapeutically effective drug with respect to patient response. The data obtained from these determinations will be correlated with the response of patients with acute leukemia to high-dose ara-C therapy. This information may be used as the objective basis for altering subsequent patient treatment on an individual basis. The data obtained will be evaluated with the view of developing tests that may be predictive of patient response and of remission duration.